Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral administration of interleukin-1 (IL-1) is known to activate the hypothalamo-pituitary-adrenal axis (HPA axis) and brain noradrenergic systems. We studied the relationship between these responses using in vivo microdialysis to assess the release of hypothalamic norepinephrine (NE), while simultaneously sampling blood for ACTH and corticosterone, and monitoring body temperature and behavior in freely moving rats. Rats were implanted with microdialysis probes in the medial hypothalamus, with intravenous catheters, and with telethermometers in the abdomen. Each rat was injected with saline and IL-1beta (1 microg ip) in random order, monitoring microdialysate NE, body temperature and plasma ACTH and corticosterone for 2-4 h after injection. Saline injections were followed by transient increases in microdialysate NE and in plasma ACTH and corticosterone. IL-1beta injections resulted in prolonged elevations of microdialysate NE, as well as plasma ACTH and corticosterone, and body temperature. IL-1beta also induced shivering and a prolonged depression of locomotor activity. Pretreatment with indomethacin (10 mg/kg sc) prevented the IL-1beta-induced increases in body temperature and the apparent increase in hypothalamic NE release, but only attenuated the IL-1beta-induced shivering and the increase in plasma ACTH. The results indicate a close temporal relationship between the release of NE and HPA axis activation. Such a relationship is also supported by the similar effects of indomethacin pretreatment on NE and ACTH. The shivering is likely involved in the increase in body temperature, but indomethacin only attenuated the shivering while it blocked the fever. However, the effects of indomethacin clearly indicate that neither the increase in body temperature nor the increase in hypothalamic NE release was essential for HPA axis activation. These results suggest that hypothalamic NE is involved in the IL-1-induced HPA axis activation, but that this is not the only mechanism by which the HPA axis is activated by intraperitoneally injected IL-1.
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PMID:Relationships among the behavioral, noradrenergic, and pituitary-adrenal responses to interleukin-1 and the effects of indomethacin. 1633 Jan 80

Stress is recognized to precipitate depressive illness, yet the specific relationship between stress, glucocorticoids and depression is not well understood. We have recently shown that repeated corticosterone (CORT) injections reliably increase depression-like behavior on the forced-swim test in rats, suggesting that glucocorticoids can precipitate depressive symptomatology. The purpose of this experiment was to determine the extent to which the effects of CORT on depression-like behavior depend on (1) the dose-injected and (2) the duration of treatment. Rats received either acute or repeated injections of vehicle, 10, 20 or 40 mg/kg of CORT, and then were subjected to the forced-swim test. Serum CORT levels were assessed after the 21-day injection period, and 30 and 60 min after the onset of forced-swim testing. Repeated, but not acute, CORT injections decreased body weight and increased immobility behavior in the forced-swim test in a dose-dependent manner. In addition, all doses of repeated CORT injections suppressed CORT release after the novel stress of forced-swim testing. Our results demonstrate that glucocorticoids increase depression-like behavior in rats in a dose-dependent manner and disrupt normal HPA axis function. These results support the hypothesis that high levels of cortisol contribute to the etiology of depressive symptomatology in humans.
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PMID:Effect of different doses of corticosterone on depression-like behavior and HPA axis responses to a novel stressor. 1638 19

Withdrawal from repeated amphetamine (AMPH) administration leads to behavioral sensitization following a drug or a stress challenge and is commonly used to model anhedonia in rats, a core symptom of depression in humans. It is proposed that corticosteroids are involved in the mediation of sensitization and depression. The aim of the present study was to investigate stress and AMPH- induced release of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) during withdrawal from an escalating dosage schedule of AMPH known to produce depression-like effects in rats. Wistar rats were given 3 injections (i.p.) per day over 3 days, escalating from 1 mg/kg to 9 mg/kg and a final injection of 10 mg/kg AMPH or saline on day 4. On day 2 of withdrawal, the animals were tested in the Porsolt swim test. HPA axis activity in response to restraint stress was tested on withdrawal day 14 and in response to AMPH challenge on withdrawal day 30. We found no effect of AMPH withdrawal in the Porsolt swim test and on the ACTH or CORT response following restraint stress. AMPH withdrawn animals expressed behavioral sensitization in terms of locomotion and reduced ACTH and CORT plasma levels following a 1 mg/kg AMPH challenge in comparison to the controls. We conclude that there is no critical involvement of a sensitized HPA axis stress response in the long-term expression of behavioral sensitization.
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PMID:Amphetamine withdrawal leads to behavioral sensitization and reduced HPA axis response following amphetamine challenge. 1656 58

Hepatitis C viral infection is a global health problem that affects approximately 4 million people in the United States. Combination treatment with pegylated interferon (IFN)-alpha plus ribavirin has been shown to be most effective in treating patients with chronic hepatitis C (CHC). Despite its efficacy, one of the most common side effects of this regimen is depression. Whereas IFN-alpha has been found to induce depression in chronic myelogenous leukemia, melanoma, and renal cell carcinoma, CHC patients may be especially prone to develop IFN-induced depression. This review includes a summary of differences between IFN-alpha and IFN-beta and addresses whether pegylation of IFN (versus nonpegylated IFN) gives rise to a treatment with reduced potential to induce depressive symptoms. Consideration is also given to evidence showing that treatment with ribavirin may contribute to IFN-induced depression. Thyroid disorders and anemia (as well as other medical conditions) have also been associated with IFN exposure and may account for some incidences of depression in CHC patients. Evidence is reviewed indicating that prior psychiatric and mood disorders (especially previous episodes of major depressive disorder), just prior to IFN treatment, contribute to the propensity to develop depression during treatment. In addition, a brief description is provided of potential biological mechanisms of IFN-induced depression (ie, monoamines, hypothalamic-pituitary-adrenocortical [HPA] axis, proinflammatory cytokines, peptidases, intercellular adhesion molecule-1, and nitric oxide). Finally, a discussion is provided on the use of antidepressants as a preventative versus restorative treatment, including a commentary on risks of using antidepressants in this patient population.
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PMID:Interferon-induced depression in chronic hepatitis C: a review of its prevalence, risk factors, biology, and treatment approaches. 1741 17

Several studies have investigated the association between burnout and HPA-axis functioning, but the results are far from consistent. This does not preclude the possibility that within a group of burnout patients a recovery of symptoms in a longitudinal course corresponds to (changes in) cortisol parameters. The latter possibility is tested in the present study before and after treatment, and at follow-up. HPA-axis functioning and burnout complaints were assessed in burned-out participants at baseline (n=74), post-treatment (n=62) and at follow-up (n=53). Multilevel regression analysis was used to test the hypothesis. Burnout complaints were significantly reduced at 8.5 months post-treatment, but there was no further reduction in complaints at follow-up 6.3 months later. Cortisol after awakening, and after dexamethasone intake showed no changes from baseline to post-treatment and follow-up. There was a small decline in cortisol during the day over the longitudinal course. The cortisol level after awakening in the longitudinal course showed significant positive association with the initial exhaustion level, a negative association with the change in the burnout exhaustion score, and a positive association with the change in depression. Although these associations are statistically significant, they only explain a small fraction of the variance in cortisol after awakening between and within persons. This implies that changes at symptom level are hardly related to changes in cortisol functioning, therefore the clinical implications of this finding are limited.
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PMID:A longitudinal study on cortisol and complaint reduction in burnout. 1669 85

Hippocampus plays a crucial role in learning and memory and, in spite of its remarkable plasticity, it is also particularly sensitive to stress hormones due to its high concentration of corticosteroid receptors. Indeed, adrenal steroids modulate hippocampal plasticity, acting on excitability and long term potentiation or depression. By a chronobiological approach, we studied the cortisol and DHEAS secretion in clinically healthy old subjects and in age-matched demented patients, including both the degenerative and the vascular type. When compared to young controls, both clinically healthy elderly subjects and demented patients, particularly those with AD, had significantly higher cortisol levels at night time, i.e. at the moment of the maximal sensitivity of HPA axis to stimulatory or inhibitory inputs. At the same time, a clear age- and disease-dependent reduction of DHEAS secretion was found. Thus the cortisol to DHEAS molar ratio was significantly higher in healthy old subjects, and even more in demented patients, when compared to young controls, and significantly linked to both age and cognitive impairment. Finally, the quantitative and qualitative changes of the adrenal secretory pattern were significantly correlated with the decline of hippocampal volumes, measured by MRI. In conclusion, several lines of evidence deal with a pathogenetic role of stress hormones in the occurrence and progression of cognitive disorders in elderly subjects. The consequent hippocampal neuronal impairment may in turn be responsible for the continuous activation of HPA axis and the increased hypothalamic expression of vasopressin and corticotropin releasing hormone.
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PMID:Stress and dementia: the role of the hypothalamicpituitary-adrenal axis. 1670 89

Pain and depression are often associated. The frequency of pain complaints in depressed patients is 13-100%. In general, depressed patients have a higher pain threshold than do controls, but lower and unchanged thresholds have also been observed. The frequency of depression in chronic pain patients is 1.5-100%. Pain etiology, short education, marital status, gender, psychiatric family history and unemployment are risk factors for depression. Possible mechanisms underlying the pathophysiology of depression and pain could be involvement of the monoamines (5-HT and NA) and the HPA axis.
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PMID:[Pain and depression]. 1676 96

Anxiety disorders are a group of mental disorders that include generalized anxiety disorder (GAD), panic disorder, phobic disorders (e.g., specific phobias, agoraphobia, social phobia) and posttraumatic stress disorder (PTSD). Anxiety disorders are among the most common of all mental disorders and, when coupled with an awareness of the disability and reduced quality of life they convey, they must be recognized as a serious public health problem. Over 20 years of preclinical studies point to a role for the CRF system in anxiety and stress responses. Clinical studies have supported a model of CRF dysfunction in depression and more recently a potential contribution to specific anxiety disorders (i.e., panic disorder and PTSD). Much work remains in both the clinical and preclinical fields to inform models of CRF function and its contribution to anxiety. First, we will review the current findings of CRF and HPA axis abnormalities in anxiety disorders. Second, we will discuss startle reflex measures as a tool for translational research to determine the role of the CRF system in development and maintenance of clinical anxiety.
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PMID:Role of corticotropin releasing factor in anxiety disorders: a translational research perspective. 1687 Jan 85

Corticotropin-releasing factor (CRF) and the related urocortin peptides mediate behavioral, cognitive, autonomic, neuroendocrine and immunologic responses to aversive stimuli by activating CRF(1) or CRF(2) receptors in the central nervous system and anterior pituitary. Markers of hyperactive central CRF systems, including CRF hypersecretion and abnormal hypothalamic-pituitary-adrenal axis functioning, have been identified in subpopulations of patients with anxiety, stress and depressive disorders. Because CRF receptors are rapidly desensitized in the presence of high agonist concentrations, CRF hypersecretion alone may be insufficient to account for the enhanced CRF neurotransmission observed in these patients. Concomitant dysregulation of mechanisms stringently controlling magnitude and duration of CRF receptor signaling also may contribute to this phenomenon. While it is well established that the CRF(1) receptor mediates many anxiety- and depression-like behaviors as well as HPA axis stress responses, CRF(2) receptor functions are not well understood at present. One hypothesis holds that CRF(1) receptor activation initiates fear and anxiety-like responses, while CRF(2) receptor activation re-establishes homeostasis by counteracting the aversive effects of CRF(1) receptor signaling. An alternative hypothesis posits that CRF(1) and CRF(2) receptors contribute to opposite defensive modes, with CRF(1) receptors mediating active defensive responses triggered by escapable stressors, and CRF(2) receptors mediating anxiety- and depression-like responses induced by inescapable, uncontrollable stressors. CRF(1) receptor antagonists are being developed as novel treatments for affective and stress disorders. If it is confirmed that the CRF(2) receptor contributes importantly to anxiety and depression, the development of small molecule CRF(2) receptor antagonists would be therapeutically useful.
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PMID:Corticotropin releasing factor (CRF) receptor signaling in the central nervous system: new molecular targets. 1691 97

Lithium augmentation refers to the addition of lithium to an antidepressant in the acute treatment phase of patients with depressive episodes who have failed to respond satisfactorily to treatment with antidepressant monotherapy. This article reviews the clinical evidence and hypotheses on the mode of action of lithium augmentation. For this purpose, studies were identified by searching Medline and by scanning the references of published reviews and standard textbooks. With regard to efficacy, 28 prospective studies (with a total of 838 depressed patients) were identified. The majority of randomized controlled trials has demonstrated substantial efficacy of lithium augmentation. A recent meta-analysis including only double-blind, placebo-controlled trials (N = 9) provided firm evidence that lithium augmentation has a statistically significant effect on response rate compared to placebo, and showed that lithium augmentation should be administered for at least 2 weeks to allow assessment of the patient's response. A recent double-blind, placebo-controlled trial revealed that responders to lithium augmentation should be maintained on the lithium-antidepressant combination for a minimum of 12 months. From animal studies there is robust evidence that lithium augmentation increases serotonin (5-HT) neurotransmission, possibly through a synergistic action of lithium and the antidepressant on brain 5-HT pathways. Neuroendocrine studies in humans on the effects of lithium augmentation on the HPA system showed an unexpected and marked increase in the ACTH and cortisol response in the combined dexamethasone/CRH test. These results are in contrast to the established decline of HPA system activity during treatment with antidepressants. In conclusion, lithium is the foremost and most well-documented augmentation strategy in refractory depression. In international treatment guidelines and algorithms, lithium augmentation is considered a first-line treatment strategy for patients with a major depressive episode who do not adequately respond to standard antidepressant treatment.
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PMID:Efficacy and mechanisms of action of lithium augmentation in refractory major depression. 1691 27


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